Epidemiological evidence supports a close relationship between respiratory viral infections and exacerbations of asthma, resulting in an increased need for medication and a decrease in pulmonary function. My laboratory is interested in the influence of murine cytomegalovirus (MCMV), an opportunistic respiratory pathogen, on asthma. To investigate this problem, we have used a mouse model of ovalbumin-induced allergic airway disease (AAD), which mimics many characteristics of human asthma. We have demonstrated that during the acute stages of AAD, concomitant MCMV infection altered the balance of Th1/Th2 cytokines, resulting in a decrease in Th2 cytokines and a delay airway eosinophilia. IL-5 is a Th2 cytokine that is important in the differentiation and maturation of eosinophils. IL-5 also possesses chemoattractant activity, resulting in the recruitment of eosinophils to the lung. While CD4+ T cells are believed to be the major source of IL-5 in AAD, we were surprised to find that bronchial epithelial cells (BECs) also contribute to IL-5 production. BECs isolated from AAD mice expressed elevated levels of IL-5 mRNA and protein. In contrast, no increase in IL-5 was noted in BECs isolated from MCMV/AAD mice.

The bronchial epithelium functions as a protective barrier between the external and internal environment of the lung, preventing the passage of airborne irritants, allergens, and pathogens. The epithelium is not passive by nature, but can release a number of specific cytokines and chemokines. Can IL-5 production by BECs increase airway eosinophilia during the acute stage of AAD or enhance airway remodeling during the chronic stage of disease? How is IL-5 production stimulated in BECs? How does MCMV infection influence IL-5 production by BECs? Do other viral respiratory pathogens alter IL-5 production in a similar manner? To address these questions, our current studies are focused on the generation of IL-5 deficient bone marrow chimeric mice, the progression of AAD in specific knock-out mice, and the growth of BECs in vitro under conditions of air-liquid interphase. Taken together, these studies will help define the role of IL-5 produced by BECs in AAD and provide insight into the mechanisms of IL-5 regulation.

Wu, C.A., Puddington, L., Whiteley, H.E., Yiamouyiannis, C.A., Mohammadu, F., and Thrall, R.S. 2001. Murine cytomegalovirus infection alters Th1/Th2 cytokine expression, decreases airway eosinophilia, and enhances mucus production in allergic airway disease. J. Immunol. 167, 2798-2807.

Schramm, C.M., L Puddington, Wu, C.A., Guernsey, L., Gharaee-Kermani, M., Phan, S.H., and Thrall, R.S. 2004. Chronic inhaled ovalbumin exposure induces antigen-dependent but not antigen-specific inhalational tolerance in a murine model of allergic airway disease. Am. J. Path. 164:295-304.

Cloutier, M.M., Guernsey, L., Wu, C.A., and Thrall, R.S. 2004. Electrophysiologic properties of the airway epithelium in the murine ovalbumin model of allergic airway disease. Am. J. Path. 164:1849-1856.